Calprotectin, a Biomarker of COVID-19 Severity (CALPRO)

NCT04953312 | Withdrawn

• 2 other identifiers: APHP2105222021-A00674-37
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to provide new insights into the pathophysiology of emergency hematopoiesis detected in severe COVID-19 patients. The investigators aim to explore the ability of calprotectin to induce an immunosuppressive myeloid program at the hematopoietic stem and progenitor cell (HSPC) level, and to identify the receptor(s) involved in this effect. Since patients with a hematological malignancy demonstrate a very high propensity to develop a severe COVID-19, the investigators will explore how HSPCs collected from patients with a myeloid malignancy respond to calprotectin.

Conditions

Severe/Moderate Coronavirus; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndromes; Old Age

Keywords

Calprotectin; hematopoiesis; COVID-19

Outcome Measures

Primary Outcomes (1)

• Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq

  Hematopoietic stem and progenitor cells from patients with severe or moderate COVID-19 or chronic myeloid malignancies or controls will be purified for analyses of transcriptome and chromatin conformation, and also functionally characterized using in vitro culture systems. Results will be compared between the three groups.

  12 months

Secondary Outcomes (1)

• Ex vivo testing of calprotectin-receptor interaction inhibitor

  During the last 6 months of the study

Study Arms (3)

COVID-19 patients (group 1)

EXPERIMENTAL

Patients with a recent diagnosis (\<7 days since first symptoms) of moderate or severe COVID-19

Biological: Blood samples

Chronic myeloid malignancies (group 2)

EXPERIMENTAL

Adults with chronic myeloid malignancies including myelodysplastic syndromes with low risk MDS ; high risk MDS according to IPSS-R or with dysplastic or proliferative chronic myelomonocytic leukemia according to WHO2016

Biological: Blood samples

Control group (group 3)

OTHER

Age-matched healthy donors

Biological: Blood samples

Interventions

Blood samples BIOLOGICAL

blood

COVID-19 patients (group 1); Chronic myeloid malignancies (group 2); Control group (group 3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Criteria for all groups:
• Adults ≥ 18 years
• Dated and signed inform consent \*
• Affiliation with a social security scheme
• Criteria for control group:
• Age-matched healthy donors
• Criteria for chronic myeloid malignancies:
• A diagnosis of low or high-risk myelodysplastic syndromes according to the WHO 2016 classification
• A diagnosis of dysplastic or proliferative chronic myelomonocytic leukemia according to WHO 2016
• Criteria for COVID-19 patients:
• Patients with a recent diagnosis (\<7 days since first symptoms) of moderate or severe COVID-19

You may not qualify if:

• Pregnant women
• Minor patient or major under protection
• Patients with COVID-19 infection and active cancer or a history of cancer within the last 6 months
• Patients with COVID-19 and severe comorbidities including cardiovascular or respiratory diseases, unbalanced diabetes, obesity (IMC \>29)
• Patient on AME (state medical aid)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Gustave Roussy Institut

Villejuif, 94800, France

Location

Related Publications (8)

• Silvin A, Chapuis N, Dunsmore G, Goubet AG, Dubuisson A, Derosa L, Almire C, Henon C, Kosmider O, Droin N, Rameau P, Catelain C, Alfaro A, Dussiau C, Friedrich C, Sourdeau E, Marin N, Szwebel TA, Cantin D, Mouthon L, Borderie D, Deloger M, Bredel D, Mouraud S, Drubay D, Andrieu M, Lhonneur AS, Saada V, Stoclin A, Willekens C, Pommeret F, Griscelli F, Ng LG, Zhang Z, Bost P, Amit I, Barlesi F, Marabelle A, Pene F, Gachot B, Andre F, Zitvogel L, Ginhoux F, Fontenay M, Solary E. Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19. Cell. 2020 Sep 17;182(6):1401-1418.e18. doi: 10.1016/j.cell.2020.08.002. Epub 2020 Aug 5.

  PMID: 32810439 BACKGROUND

• Shi H, Zuo Y, Yalavarthi S, Gockman K, Zuo M, Madison JA, Blair C, Woodward W, Lezak SP, Lugogo NL, Woods RJ, Lood C, Knight JS, Kanthi Y. Neutrophil calprotectin identifies severe pulmonary disease in COVID-19. J Leukoc Biol. 2021 Jan;109(1):67-72. doi: 10.1002/JLB.3COVCRA0720-359R. Epub 2020 Sep 1.

  PMID: 32869342 BACKGROUND

• Udeh R, Advani S, de Guadiana Romualdo LG, Dolja-Gore X. Calprotectin, an Emerging Biomarker of Interest in COVID-19: A Systematic Review and Meta-Analysis. J Clin Med. 2021 Feb 15;10(4):775. doi: 10.3390/jcm10040775.

  PMID: 33672040 BACKGROUND

• Abers MS, Delmonte OM, Ricotta EE, Fintzi J, Fink DL, de Jesus AAA, Zarember KA, Alehashemi S, Oikonomou V, Desai JV, Canna SW, Shakoory B, Dobbs K, Imberti L, Sottini A, Quiros-Roldan E, Castelli F, Rossi C, Brugnoni D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Castagnoli R, Montagna D, Licari A, Marseglia GL, Gliniewicz EF, Shaw E, Kahle DE, Rastegar AT, Stack M, Myint-Hpu K, Levinson SL, DiNubile MJ, Chertow DW, Burbelo PD, Cohen JI, Calvo KR, Tsang JS; NIAID COVID-19 Consortium; Su HC, Gallin JI, Kuhns DB, Goldbach-Mansky R, Lionakis MS, Notarangelo LD. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight. 2021 Jan 11;6(1):e144455. doi: 10.1172/jci.insight.144455.

  PMID: 33232303 BACKGROUND

• Bauer W, Diehl-Wiesenecker E, Ulke J, Galtung N, Havelka A, Hegel JK, Tauber R, Somasundaram R, Kappert K. Outcome prediction by serum calprotectin in patients with COVID-19 in the emergency department. J Infect. 2021 Apr;82(4):84-123. doi: 10.1016/j.jinf.2020.11.016. Epub 2020 Nov 17. No abstract available.

  PMID: 33217473 BACKGROUND

• Luis Garcia de Guadiana Romualdo, Mulero MDR, Olivo MH, Rojas CR, Arenas VR, Morales MG, Abellan AB, Conesa-Zamora P, Garcia-Garcia J, Hernandez AC, Morell-Garcia D, Dolores Albaladejo-Oton M, Consuegra-Sanchez L. Circulating levels of GDF-15 and calprotectin for prediction of in-hospital mortality in COVID-19 patients: A case series. J Infect. 2021 Feb;82(2):e40-e42. doi: 10.1016/j.jinf.2020.08.010. Epub 2020 Aug 12. No abstract available.

  PMID: 32795482 BACKGROUND

• Mahler M, Meroni PL, Infantino M, Buhler KA, Fritzler MJ. Circulating Calprotectin as a Biomarker of COVID-19 Severity. Expert Rev Clin Immunol. 2021 May;17(5):431-443. doi: 10.1080/1744666X.2021.1905526. Epub 2021 Apr 13.

  PMID: 33750254 BACKGROUND

• Kaya T, Yaylaci S, Nalbant A, Yildirim I, Kocayigit H, Cokluk E, Sekeroglu MR, Koroglu M, Guclu E. Serum calprotectin as a novel biomarker for severity of COVID-19 disease. Ir J Med Sci. 2022 Feb;191(1):59-64. doi: 10.1007/s11845-021-02565-8. Epub 2021 Feb 27.

  PMID: 33641087 BACKGROUND

Related Links

• Groupe Francophone des Myélodysplasies: GFM is a cooperative group of the French Society of Hematology

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; COVID-19

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Michaela FONTENAY, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Eric SOLARY, MD

  Gustave Roussy Institut

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2021
• First Posted: July 7, 2021
• Study Start: January 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: July 1, 2024
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)